# Polyphenol-rich Chinese olive extracts attenuate lipid accumulation in HepG2 cells, accompanied by AMPK phosphorylation and miRNA alterations

**Authors:** Hong Wang, Bingqi Huang, Wenhong Zhao, Gongliang Liu, Weidong Bai

PMC · DOI: 10.3389/fnut.2026.1749622 · Frontiers in Nutrition · 2026-02-11

## TL;DR

Chinese olive extracts reduce fat buildup in liver cells by activating AMPK and changing miRNA levels, suggesting potential for functional foods.

## Contribution

The study identifies a novel lipid-lowering mechanism of Chinese olive polyphenols involving AMPK and miRNA modulation.

## Key findings

- Chinese olive extracts reduced intracellular lipid and triglyceride levels in HepG2 cells.
- Extract treatment modulated genes related to lipogenesis and β-oxidation.
- AMPK phosphorylation and miR-122/miR-21 downregulation were observed with extract treatment.

## Abstract

Chinese olive (Canarium album L.) is a rich source of phenolic compounds and has been suggested to exhibit distinct lipid-lowering bioactivities from those reported for Mediterranean olive polyphenols.

This study investigated the effects of polyphenol-rich Chinese olive extracts on sodium oleate-induced lipid accumulation in HepG2 cells.

Treatment with extracts was associated with a significant reduction in intracellular total lipid and triglyceride levels in a concentration-dependent manner. RT-qPCR results revealed that extract treatment was accompanied by the downregulation of lipogenesis-related genes (SREBP-1c, ACC1, FASN, and DGAT2) and the upregulation of β-oxidation-associated genes (PGC-1α, PPARα, CPT-1A, and ACOX1). Western blot analysis showed that extract treatment was associated with AMPK phosphorylation, occurring concurrently with the observed lipid-associated changes. Furthermore, treatment with extracts was accompanied by decreased expression of miR-122 and miR-21, which correlated with the expression of their respective lipid-metabolism target genes. UPLC–MS/MS analysis identified 39 phenolic compounds in the extract, including methyl brevifolincarboxylate and ellagic acid derivatives, indicating a complex phenolic composition.

These results demonstrate that attenuation of lipid accumulation by polyphenol-rich Chinese olive extracts in HepG2 cells is accompanied by AMPK phosphorylation and miRNA modulation. This finding supports the potential of Chinese olive extracts as a natural hepatoprotective ingredient for the development of functional foods and nutraceuticals.

## Linked entities

- **Genes:** Srebf1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 78968], ACACA (acetyl-CoA carboxylase alpha) [NCBI Gene 31], FASN (fatty acid synthase) [NCBI Gene 2194], DGAT2 (diacylglycerol O-acyltransferase 2) [NCBI Gene 84649], PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891], PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465], CPT1A (carnitine palmitoyltransferase 1A) [NCBI Gene 1374], ACOX1 (acyl-CoA oxidase 1) [NCBI Gene 51]
- **Chemicals:** methyl brevifolincarboxylate (PubChem CID 5319518), ellagic acid (PubChem CID 5281855)

## Full-text entities

- **Genes:** ACTBP (actin beta pseudogene) [NCBI Gene 281594], PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, BCL2A1 (BCL2 related protein A1) [NCBI Gene 597] {aka ACC-1, ACC-2, ACC1, ACC2, BCL2L5, BFL1}, SREBF1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 6720] {aka HMD, IFAP2, SREBP1, bHLHd1}, Dgat2 (diacylglycerol O-acyltransferase 2) [NCBI Gene 67800] {aka 0610010B06Rik, ARAT, DGAT-2}, Mir21a (microRNA 21a) [NCBI Gene 387140] {aka Mir21, Mirn21, mmu-mir-21, mmu-mir-21a}, DGAT2 (diacylglycerol O-acyltransferase 2) [NCBI Gene 84649] {aka ARAT, GS1999FULL, HMFN1045}, CPT1A (carnitine palmitoyltransferase 1A) [NCBI Gene 1374] {aka CPT I, CPT1, CPT1-L, CPTI-L, L-CPT1}, ACACA (acetyl-CoA carboxylase alpha) [NCBI Gene 31] {aka ACAC, ACACAD, ACACalpha, ACC, ACC1, ACCA}, Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 19013] {aka 4933429D07Rik, Nr1c1, PPAR-alpha, PPARalpha, Ppar}, ACOX1 (acyl-CoA oxidase 1) [NCBI Gene 51] {aka ACOX, AOX, MITCH, PALMCOX, SCOX}, Srebf1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 20787] {aka ADD1, SREBP1, bHLHd1}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, AWAT1 (acyl-CoA wax alcohol acyltransferase 1) [NCBI Gene 158833] {aka DGA2, DGAT2L3}, Hmgcr (3-hydroxy-3-methylglutaryl-Coenzyme A reductase) [NCBI Gene 15357] {aka HMG-CoAR, Red}, Mir122 (microRNA 122) [NCBI Gene 387231] {aka Mir122a, Mir122b, Mirn122a, Mirn122b, mir-122, mmu-mir-122}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, MIR122 (microRNA 122) [NCBI Gene 406906] {aka MIR122A, MIRN122, MIRN122A, hsa-mir-122, miRNA122, miRNA122A}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}
- **Diseases:** metabolic disorders (MESH:D008659), fatty liver (MESH:D005234), NAFLD (MESH:D065626), diabetic (MESH:D003920), inflammatory (MESH:D007249), hyperlipidemia (MESH:D006949), metabolic syndrome (MESH:D024821), chronic diseases (MESH:D002908), cytotoxicity (MESH:D064420), cardiovascular disease (MESH:D002318)
- **Chemicals:** ethanol (MESH:D000431), Sodium oleate (MESH:C013173), cholesterol (MESH:D002784), hydroxytyrosol (MESH:C005975), isopropanol (MESH:D019840), SDS (MESH:D012967), acetic acid (MESH:D019342), penicillin G (MESH:D010400), free fatty acids (MESH:D005230), phenolic acids (MESH:C017616), acetyl-CoA. (MESH:D000105), hyperoside (MESH:C021304), Oil Red O (MESH:C011049), terpenoids (MESH:D013729), water (MESH:D014867), phospholipids (MESH:D010743), methylene blue (MESH:D008751), kaempferol (MESH:C006552), acetonitrile (MESH:C032159), TG (MESH:D014280), streptomycin (MESH:D013307), quercetin (MESH:D011794), formic acid (MESH:C030544), salicylic acid (MESH:D020156), gallic acid (MESH:D005707), formaldehyde (MESH:D005557), glucose (MESH:D005947), DMSO (MESH:D004121), Flavonoids (MESH:D005419), glutaraldehyde (MESH:D005976), Tween 20 (MESH:D011136), PBS (MESH:D007854), coumarins (MESH:D003374), diacylglycerol (MESH:D004075), PVDF (MESH:C024865), ellagic acid (MESH:D004610), Lipid (MESH:D008055), luteolin-7-O-glucoside (MESH:C066408), Polyphenol (MESH:D059808), CO2 (MESH:D002245), SYBR Green (MESH:C098022), methyl brevifolincarboxylate (MESH:C087786), tannins (MESH:D013634), Fatty acid (MESH:D005227), carbohydrates (MESH:D002241), lignans (MESH:D017705), isoquercitrin (MESH:C016527), penicillin (MESH:D010406), Chinese olive extract (-)
- **Species:** Canarium vulgare (Java almond, species) [taxon 246350], Olea (olives, genus) [taxon 4145], Mus musculus (house mouse, species) [taxon 10090], Olea europaea (common olive, species) [taxon 4146], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12932180/full.md

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932180/full.md

## References

108 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932180/full.md

---
Source: https://tomesphere.com/paper/PMC12932180